The aim of this project is to study the development of hypertrophy in an integrated fashion. Using thyrotoxicosis in dogs as a model for hypertrophy, this project will examine the roles of heart rate, sympathetic stimulation, hypertension, and chronic volume overload in the development of hypertrophy by causing interventions which will alter these factors in thyrotoxicosis and by comparing interventions to thyrotoxicosis. Parameters to be examined include hemodynamic alterations caused by hypertrophy, changes in alpha, beta, and cholinergic receptors, myosin phosphorylation, and baroreceptor reflexes. Dogs chronically instrumented to measure left ventricular, aortic and left atrial pressures and their derivatives, aortic flow, left ventricular diameter, volumes and mass will be made thyrotoxic and then have heart rate altered by right stellate ganglionectomy and/or vagotomy to return heart rate to control levels to evaluate its effect. Chronic atrioventricular sequential pacing will also be performed to compare increased heart rate alone to thyrotoxicosis. Chronic propranolol therapy will be compared to heart rate reduction to examine the effect of sympathetic stimulation on the left ventricle independent of heart rate suppression. Hypertension and chronic volume overload will be compared to similar levels of each during thyrotoxicosis. Baroreceptor reflexes will be examined during hypertrophy by volume loading, unloading, and left atrial distention. These studies should give new insight into hypertrophy, its causes, and may provide information for prevention.